Medication after complete removal of stage III (or high-risk stage II) melanoma to lower the chance of recurrence
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When a melanoma has reached the lymph nodes, the surgeon can usually remove all of it that can be seen or felt. The concern afterward is not what was taken out but what might have been left behind: a small number of melanoma cells too few to show up on any scan. Adjuvant therapy is medication given after that surgery to find and destroy those cells before they can grow into a new tumor.
A decade ago there was no treatment after melanoma surgery that reliably lowered the risk of recurrence. Today there are several, and for many people with stage III melanoma a year of adjuvant immunotherapy or targeted therapy is now a standard offer. This page explains who it is for, what the choices are, what the trials found, and how to weigh the benefit against the side effects.
Adjuvant therapy is given after surgery. Giving the same kind of medication before surgery is a newer strategy covered separately in neoadjuvant immunotherapy for melanoma.
Adjuvant comes from a Latin word meaning "to help." An adjuvant treatment is not the main treatment — surgery is — but an add-on meant to make surgery more likely to succeed in the long run. The logic is straightforward:
Adjuvant therapy does not help everyone who receives it. Some people were already cured by surgery alone and take the medication without needing it; others recur despite it. Because there is no test that shows in advance which group a person is in, the decision rests on the average benefit seen in large trials, weighed against the side effects an individual would face.
Eligibility is defined by stage after all known melanoma has been surgically removed:
Which substage applies to you depends on the primary tumor and on what the nodes showed — see sentinel lymph node biopsy and what your melanoma stage means.
There are two families of adjuvant medication for melanoma. Both are usually given for about one year.
These drugs release a brake on the immune system so it can recognize and kill melanoma cells. They are given as an intravenous infusion every few weeks.
The two anti-PD-1 drugs have not been compared head to head in the adjuvant setting and are considered interchangeable in practice.
For the roughly 40 to 50 percent of melanomas that carry a BRAF V600 mutation, the oral pair dabrafenib plus trametinib is an adjuvant option for resected stage III disease, studied in the COMBI-AD trial. It is taken as pills every day for a year. Your melanoma tissue has to be tested for the BRAF mutation first; this option does not apply if the mutation is absent. Targeted therapy is covered in more depth in BRAF/MEK targeted therapy for melanoma.
Across CheckMate 238, KEYNOTE-054, KEYNOTE-716, and COMBI-AD, the consistent finding is an improvement in recurrence-free survival — the length of time people stay free of any return of melanoma. In each trial, fewer people had recurred at the two- to three-year mark in the treatment group than in the comparison group, and the separation between the groups has held up with longer follow-up.
The picture for overall survival — whether adjuvant therapy helps people live longer, not just longer without recurrence — is less settled. Some trials were designed in a way that makes this hard to measure, because people whose melanoma came back could then receive effective treatment, including the same class of drug. As of the latest reports, a clear overall-survival advantage has not been demonstrated for adjuvant anti-PD-1 immunotherapy, and results are still maturing.
A reasonable summary: adjuvant therapy reliably delays or prevents recurrence for a meaningful share of people, and recurrence is easier to treat when it is caught as a small-volume problem — but the treatment is not a guarantee, and its effect on lifespan is still being worked out.
The decision comes down to comparing two things: how likely your melanoma is to return, and how much of a burden the treatment would be for you.
Stage III is not one risk. A person with stage IIIA melanoma (a tiny deposit in one sentinel node) has a much lower chance of recurrence than someone with stage IIIC or IIID (bulky or multiple involved nodes, or in-transit disease). The higher the baseline risk, the more absolute benefit a fixed percentage improvement translates into — and the easier the decision to treat. For lower-risk substages, the benefit is smaller and the side-effect trade-off weighs more heavily.
Anti-PD-1 drugs are generally better tolerated than older melanoma treatments, but because they work by loosening restraints on the immune system, they can cause it to attack healthy tissue — the thyroid, the skin, the bowel, the liver, the joints, the lungs. Most of these immune-related side effects are manageable, and serious ones usually settle when the drug is paused and steroids are started.
One matters especially in the adjuvant setting because it is permanent: damage to a hormone-producing gland. Roughly one in seven people treated with adjuvant anti-PD-1 develops an underactive thyroid, pituitary, or adrenal gland that does not recover, meaning a daily hormone-replacement pill for life. That is a modest inconvenience for many people and a significant one for others, and it is worth thinking through before starting — particularly for someone whose recurrence risk is on the lower side.
Targeted therapy has a different profile: fevers, chills, fatigue, joint aches, and rash are common while on the pills but generally resolve after the year is done. It is only an option if the melanoma carries a BRAF mutation.
Alongside the rise of adjuvant medication, the surgery for node-positive melanoma has become less extensive. It used to be standard that a positive sentinel node was followed by completion lymph node dissection — removing all the remaining nodes in that basin, an operation with a meaningful risk of long-term arm or leg swelling (lymphedema).
The MSLT-II trial changed that. It found that going straight to completion dissection after a positive sentinel node did not help people live longer than carefully watching those nodes with regular ultrasound and operating only if disease reappeared there. Dissection did control disease in the nodes slightly better, but at the cost of more lymphedema.
As a result, most people with a positive sentinel node today are offered nodal ultrasound surveillance rather than immediate full dissection — and adjuvant therapy is layered on top of that surveillance approach.
Adjuvant therapy after melanoma surgery is one of the clearest advances in skin cancer care of the past decade. For resected stage III melanoma, and now for high-risk resected stage II and selected resected stage IV disease, about a year of anti-PD-1 immunotherapy — or, for BRAF-mutant tumors, dabrafenib plus trametinib — measurably lowers the chance the melanoma returns.
It is not the right choice for everyone. The benefit is largest for the higher-risk substages, the overall-survival data are still maturing, and immunotherapy carries a roughly one-in-seven risk of a permanent hormone problem. This is a shared decision, best made with a melanoma oncologist who can put real numbers to your particular situation.
Disclaimer: This article is for educational purposes only and not a substitute for professional medical advice. Always consult a qualified dermatologist or oncologist about your personal diagnosis and treatment plan.
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